Crosstalk Between Metastatic Cancer Cells and the Bone Microenvironment

ABSTRACT Bone metastasis is highly prevalent in breast, prostate, and lung cancers and is strongly correlated with poor clinical outcomes and the occurrence of skeletal‐related events (SREs). Bidirectional communication between tumor cells and bone‐resident cells provides selective advantages that promote tumor growth, resulting in either bone destruction or the deposition of a new bone matrix. Current treatment strategies are predominantly palliative, underscoring the urgent need for the development of novel and more effective therapeutic targets. In this review, we summarize the key findings regarding the interactions and molecular mechanisms between cancer cells and major cellular components of the bone microenvironment, including osteoblasts, osteoclasts, endothelial cells, and immune cells. This crosstalk between metastatic cancer cells and the bone microenvironment not only promotes tumor cell survival and colonization in bone, but also modulates the activity of osteoblasts and osteoclasts and remodels the bone microenvironment. Notably, targeting these cell‐cell interactions offers promising therapeutic strategies for the prevention and treatment of bone metastasis.